Advertisement

Mitochondrial BKCa Channel as a Target for Cardioprotection

  • František Kolář
Conference paper
Part of the NATO Science for Peace and Security Series A: Chemistry and Biology book series (NAPSA)

Abstract

Large-conductance Ca2+-activated K+ channels (BKCa) are widely expressed in the plasma membrane of various types of cells and play important roles in many physiological processes by providing negative feedback for membrane depolarization and Ca2+ entry. Their mitochondrial counterparts located in the inner membrane are thought to be involved in the control of mitochondrial functions and serve as mediators of cytoprotection. This review briefly outlines basic knowledge of the molecular structure, sources of tissue diversity, and modulation of BKCa channels by endogenous and pharmacological agents. Particular attention is paid to the heart with an emphasis on the role mitochondrial BKCa channels in various forms of cardioprotection against acute ischemia/reperfusion injury.

Keywords

Ventricular Myocytes Reactive Oxygen Species Formation H9c2 Cell BKCa Channel Dehydroabietic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments 

Supported by the Czech Science Foundation (grant 303/12/1162).

References

  1. 1.
    Aldakkak M, Stowe DF, Cheng Q etal (2010) Mitochondrial matrix K+ flux independent of large conductance Ca2+-activated K+ channel opening. Am J Physiol Cell Physiol 298:C530–C541CrossRefPubMedGoogle Scholar
  2. 2.
    Aon MA, Cortassa S, Wei AC etal (2010) Energetic performance is improved by Specific activation of K+ fluxes through KCa channels in heart mitochondria. Biochim Biophys Acta 1797:71–80PubMedGoogle Scholar
  3. 3.
    Atkinson NS, Robertson GA, Ganetzky B (1991) A component of calcium-activated potassium channels encoded by the Drosophila slo locus. Science 253:551–555CrossRefPubMedGoogle Scholar
  4. 4.
    Barman SA, Zhu S, White RE (2004) PKC activates BKCa channels in rat pulmonary arterial smooth muscle via cGMP-dependent protein kinase. Am J Physiol Lung Cell Mol Physiol 286:L1275–L1281CrossRefPubMedGoogle Scholar
  5. 5.
    Bautista L, Castro MJ, Lopez-Barneo J etal (2009) Hypoxia inducible factor-2α stabilization and maxi-K+ channel β1-subunit gene repression by hypoxia in cardiac myocytes. Role in preconditioning. Circ Res 104:1364–1372CrossRefPubMedGoogle Scholar
  6. 6.
    Bentzen BH, Andersen RW, Olesen SP etal (2010) Synthesis and characterisation of NS13558: a new important tool for addressing KCa1.1 channel function exvivo. N-S Arch Pharmacol 381:271–283CrossRefGoogle Scholar
  7. 7.
    Bentzen BH, Nardi A, Calloe K etal (2007) The small molecule NS11021 is a potent and specific activator of Ca2+-activated big-conductance K+ channels. Mol Pharmacol 72:1033–1044CrossRefPubMedGoogle Scholar
  8. 8.
    Bentzen H, Osadchii O, Jespersen T etal (2009) Activation of big conductance Ca2+-activated K+ channels (BK) protects the heart against ischemia–reperfusion injury. Pflugers Arch 457:979–988CrossRefPubMedGoogle Scholar
  9. 9.
    Berkefeld H, Fakler B, Schulte U (2010) Ca2+-activated K+ channels: from protein complexes to function. Physiol Rev 90:1437–1459CrossRefPubMedGoogle Scholar
  10. 10.
    Bilmen JG, Wootton LL, Michelangeli F (2002) The mechanism of inhibition of the sarcoplasmic reticulum Ca2+ATPase by paxilline. Arch Biochem Biophys 406:55–64CrossRefPubMedGoogle Scholar
  11. 11.
    Borbouse L, Dick GM, Asano S etal (2009) Impaired function of coronary BKCa channels in metabolic syndrome. Am J Physiol Heart Circ Physiol 297:H1629–H1637CrossRefPubMedGoogle Scholar
  12. 12.
    Borchert GH, Kolar F (2011) Postconditioning induced by BKCa channel opening in isolated ventricular myocytes is mediated by reactive oxygen species. Exp Clin Cardiol 16:4AGoogle Scholar
  13. 13.
    Borchert GH, Yang C, Kolar F (2011) Mitochondrial BKCa channels contribute to protection of cardiomyocytes isolated from chronically hypoxic rats. Am J Physiol Heart Circ Physiol 300:H507–H513CrossRefPubMedGoogle Scholar
  14. 14.
    Bowles DK, Laughlin MH, Sturek M (1998) Exercise training increases K+-channel contribution to regulation of coronary arterial tone. J Appl Physiol 84:1225–1233PubMedGoogle Scholar
  15. 15.
    Brenner R, Jegla TJ, Wickenden A etal (2000) Cloning and functional characterization of novel large conductance calcium-activated potassium channel beta subunits, hKCNMB3 and hKCNMB4. J Biol Chem 275:6453–6461CrossRefPubMedGoogle Scholar
  16. 16.
    Callewaert G, Vereecke J, Carmeliet E (1986) Existence of a calcium-dependent potassium channel in the membrane of cow cardiac Purkinje cells. Pflugers Arch 406:424–426CrossRefPubMedGoogle Scholar
  17. 17.
    Candia S, Garcia ML, Latorre R (1992) Mode of action of iberiotoxin, a potent blocker of the large conductance Ca2+-activated K+ channel. Biophys J 63:583–590CrossRefPubMedGoogle Scholar
  18. 18.
    Cao CM, Chen M, Wong TM (2005) The KCa channel as a trigger for the cardioprotection induced by κ-opioid receptor stimulation–its relationship with protein kinase C. Br J Pharmacol 145:984–991CrossRefPubMedGoogle Scholar
  19. 19.
    Cao CM, Xia Q, Gao Q etal (2005) Calcium-activated potassium channel triggers cardioprotection of ischemic preconditioning. J Pharmacol Exp Ther 312:644–650CrossRefPubMedGoogle Scholar
  20. 20.
    Cheng Y, Gu XQ, Bednarczyk P etal (2008) Hypoxia increases activity of the BK-channel in the inner mitochondrial membrane and reduces activity of the permeability transition pore. Cell Physiol Biochem 22:127–136CrossRefPubMedGoogle Scholar
  21. 21.
    Cox DH, Cui J, Aldrich RW (1997) Allosteric gating of a large conductance Ca-activated K+ channel. J Gen Physiol 110:257–281CrossRefPubMedGoogle Scholar
  22. 22.
    Cui J, Yang H, Lee US (2009) Molecular mechanisms of BK channel activation. Cell Mol Life Sci 66:852–875CrossRefPubMedGoogle Scholar
  23. 23.
    Franciolini F, Hogg R, Catacuzzeno L etal (2001) Large-conductance calcium-activated potassium channels in neonatal rat intracardiac ganglion neurons. Pflugers Arch 441:629–638CrossRefPubMedGoogle Scholar
  24. 24.
    Fretwell L, Dickenson JM (2009) Role of large-conductance Ca2+-activated potassium channels in adenosine A1 receptor-mediated pharmacological preconditioning in H9c2 cells. Eur J Pharmacol 618:37–44CrossRefPubMedGoogle Scholar
  25. 25.
    Fretwell L, Dickenson JM (2011) Role of large-conductance Ca2+-activated K+ channels in adenosine A1 receptor-mediated pharmacological postconditioning in H9c2 cells. Can J Physiol Pharmacol 89:24–30CrossRefPubMedGoogle Scholar
  26. 26.
    Fukasawa M, Nishida H, Sato T etal (2008) 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol), a phosphodiesterase type 3 inhibitor, reduces infarct size via activation of mitochondrial Ca2+-activated K+ channels in rabbit hearts. J Pharmacol Exp Ther 326:100–104CrossRefPubMedGoogle Scholar
  27. 27.
    Garlid KD, Halestrap AP (2012) The mitochondrial KATP channel–fact or fiction? J Mol Cell Cardiol 52:578–583CrossRefPubMedGoogle Scholar
  28. 28.
    Gaspar T, Katakam P, Snipes JA etal (2008) Delayed neuronal preconditioning by NS1619 is independent of calcium activated potassium channels. J Neurochem 105:1115–1128CrossRefPubMedGoogle Scholar
  29. 29.
    Gessner G, Cui YM, Otani Y etal (2012) Molecular mechanism of pharmacological activation of BK channels. Proc Natl Acad Sci USA 109:3552–3557CrossRefPubMedGoogle Scholar
  30. 30.
    Ghatta S, Nimmagadda D, Xu X etal (2006) Large-conductance, calcium-activated potassium channels: structural and functional implications. Pharmacol Ther 110:103–116CrossRefPubMedGoogle Scholar
  31. 31.
    Gu XQ, Siemen D, Parvez S etal (2007) Hypoxia increases BK channel activity in the inner mitochondrial membrane. Biochem Biophys Res Commun 358:311–316CrossRefPubMedGoogle Scholar
  32. 32.
    Ha TS, Heo MS, Park CS (2004) Functional effects of auxiliary β4-subunit on rat large-­conductance Ca2+-activated K+ channel. Biophys J 86:2871–2882CrossRefPubMedGoogle Scholar
  33. 33.
    Hagen BM, Sanders KM (2006) Deglycosylation of the ß1-subunit of the BK channel changes biophysical properties. Am J Physiol Cell Physiol 291:C750–C756CrossRefPubMedGoogle Scholar
  34. 34.
    Heinen A, Aldakkak M, Stowe DF etal (2007) Reverse electron flow-induced ROS production is attenuated by activation of mitochondrial Ca2+-sensitive K+ channels. Am J Physiol Heart Circ Physiol 293:H1400–H1407CrossRefPubMedGoogle Scholar
  35. 35.
    Heinen A, Camara AKS, Aldakkak M etal (2006) Mitochondrial Ca2+-induced K+ influx increases respiration and enhances ROS production while maintaining membrane potential. Am J Physiol Cell Physiol 292:C148–C156CrossRefPubMedGoogle Scholar
  36. 36.
    Hou S, Heinemann SH, Hoshi T (2009) Modulation of BKCa channel gating by endogenous signaling molecules. Physiology 24:26–35CrossRefPubMedGoogle Scholar
  37. 37.
    Hoyer J, Distler A, Haase W etal (1994) Ca2+ influx through stretch-activated cation channels activates maxi K+ channels in porcine endocardial endothelium. Proc Natl Acad Sci USA 91:2367–2371CrossRefPubMedGoogle Scholar
  38. 38.
    Imlach WL, Finch SC, Miller JH etal (2010) A role of BK channels in heart rate regulation in rodents. PLoS One 5:e8698CrossRefPubMedGoogle Scholar
  39. 39.
    Kang SH, Park WS, Kim N etal (2007) Mitochondrial Ca2+-activated K+ channels more efficiently reduce mitochondrial Ca2+ overload in rat ventricular myocytes. Am J Physiol Heart Circ Physiol 293:H307–H313CrossRefPubMedGoogle Scholar
  40. 40.
    Katragadda D, Batchu SN, Cho WJ etal (2009) Epoxyeicosatrienoic acids limit damage to mitochondrial function following stress in cardiac cells. J Mol Cell Cardiol 46:867–875CrossRefPubMedGoogle Scholar
  41. 41.
    Kim JY, Park CS (2008) Potentiation of large-conductance calcium-activated potassium (BKCa) channels by a specific isoform of protein kinase C. Biochem Biophys Res Commun 365:459–465CrossRefPubMedGoogle Scholar
  42. 42.
    Knaus HG, Folander K, Garcia-Calvo M etal (1994) Primary sequence and immunological characterization of β-subunit of high conductance Ca2+-activated K+ channel from smooth muscle. J Biol Chem 269:17274–17278PubMedGoogle Scholar
  43. 43.
    Ko JH, Ibrahim MA, Park WS etal (2009) Cloning of large-conductance Ca2+-activated K+ channel α-subunits in mouse cardiomyocytes. Biochem Biophys Res Commun 389:74–79CrossRefPubMedGoogle Scholar
  44. 44.
    Kotlikoff MI, Kamm KE (1996) Molecular mechanism of β-adrenergic relaxation of airway smooth muscle. Annu Rev Physiol 58:115–141CrossRefPubMedGoogle Scholar
  45. 45.
    Kwan HY, Shen B, Ma X etal (2009) TRPC1 associates with BKCa channel to form signal complex in vascular smooth muscle cells. Circ Res 104:670–678CrossRefPubMedGoogle Scholar
  46. 46.
    Latorre R, Miller C (1983) Conduction and selectivity in potassium channels. J Membr Biol 71:11–30CrossRefPubMedGoogle Scholar
  47. 47.
    Longland CL, Dyer JL, Michelangeli F (2000) The mycotoxin paxilline inhibits the cerebellar inositol 1,4,5-trisphosphate receptor. Eur J Pharmacol 408:219–225CrossRefPubMedGoogle Scholar
  48. 48.
    Lu T, Ye D, He T etal (2008) Impaired Ca2+-dependent activation of large-conductance Ca2+-activated K+ channels in the coronary artery smooth muscle cells of Zucker diabetic fatty rats. Biophys J 95:5165–5177CrossRefPubMedGoogle Scholar
  49. 49.
    Malinska D, Mirandola SR, Kunz WS (2010) Mitochondrial potassium channels and reactive oxygen species. FEBS Lett 584:2043–2048CrossRefPubMedGoogle Scholar
  50. 50.
    Meera P, Wallner M, Song M etal (1997) Large conductance voltage- and calcium-dependent K+ channel, a distinct member of voltage-dependent ion channels with seven N-terminal transmembrane segments (S0-S6), an extracellular N terminus, and an intracellular (S9-S10) C terminus. Proc Natl Acad Sci USA 94:14066–14071CrossRefPubMedGoogle Scholar
  51. 51.
    Meera P, Wallner M, Toro L (2000) A neuronal β subunit (KCNMB4) makes the large conductance, voltage- and Ca2+-activated K+ channel resistant to charybdotoxin and iberiotoxin. Proc Natl Acad Sci USA 97:5562–5567CrossRefPubMedGoogle Scholar
  52. 52.
    Nardi A, Olesen SP (2008) BK channel modulators: a comprehensive overview. Curr Med Chem 15:1126–1146CrossRefPubMedGoogle Scholar
  53. 53.
    Nishimaru K, Eghbali M, Lu R etal (2004) Functional and molecular evidence of MaxiK channel β1 subunit decrease with coronary artery aging in the rat. J Physiol 559:849–862PubMedGoogle Scholar
  54. 54.
    Nishida H, Sato T, Miyazaki M etal (2008) Infarct size limitation by adrenomedullin: protein kinase A but not PI3-kinase is linked to mitochondrial KCa channels. Cardiovasc Res 77:398–405PubMedGoogle Scholar
  55. 55.
    Node K, Kitakaze M, Kosaka H etal (1997) Bradykinin mediation of Ca2+-activated K+ channels regulates coronary blood flow in ischemic myocardium. Circulation 95:1560–1567CrossRefPubMedGoogle Scholar
  56. 56.
    Nomura M, Inamura N, Nishida H etal (2008) Anandamide reduces infarct size through activation of mitochondrial Ca2+-activated K+ channels in rabbit hearts. J Mol Cell Cardiol 45:S23CrossRefGoogle Scholar
  57. 57.
    Ohya S, Kuwata Y, Sakamoto K etal (2005) Cardioprotective effects of estradiol include the activation of large-conductance Ca2+-activated K+ channels in cardiac mitochondria. Am J Physiol Heart Circ Physiol 289:H1635–H1642CrossRefPubMedGoogle Scholar
  58. 58.
    Olesen SP, Munch E, Moldt P etal (1994) Selective activation of Ca2+-dependent K+ channels by novel benzimidazolone. Eur J Pharmacol 251:53–59CrossRefPubMedGoogle Scholar
  59. 59.
    Orio P, Rojas P, Ferreira G etal (2002) New disguises for an old channel: MaxiK channel β-subunits. News Physiol Sci 17:156–161PubMedGoogle Scholar
  60. 60.
    Panyi G, Possani LD, Rodriguez de la Vega RC etal (2006) K+ channel blockers: novel tools to inhibit T cell activation leading to specific immunosuppression. Curr Pharm Des 12:2199–2220CrossRefPubMedGoogle Scholar
  61. 61.
    Park WS, Kang SH, Son YK etal (2007) The mitochondrial Ca2+-activated K+ channel activator, NS 1619 inhibits L-type Ca2+ channels in rat ventricular myocytes. Biochem Biophys Res Commun 362:31–36CrossRefPubMedGoogle Scholar
  62. 62.
    Pongs O, Schwarz JR (2010) Ancillary subunits associated with voltage-dependent K+ channels. Physiol Rev 90:755–796CrossRefPubMedGoogle Scholar
  63. 63.
    Redel A, Lange M, Jazbutyte V etal (2008) Activation of mitochondrial large-conductance calcium-activated K+ channel via protein kinase A mediates desflurane-induced preconditioning. Anesth Analg 106:384–391CrossRefPubMedGoogle Scholar
  64. 64.
    Sakamoto K, Nonomura T, Ohya S etal (2006) Molecular mechanisms for BK channel activation by a novel opener, 12,14-dichlorodehydroabietic acid. J Pharmacol Exp Ther 316:144–153CrossRefPubMedGoogle Scholar
  65. 65.
    Sakamoto K, Ohya S, Muraki K etal (2008) A novel opener of large-conductance Ca2+-activated K+ (BK) channel reduces ischemic injury in rat cardiac myocytes by activating mitochondrial KCa channel. J Pharmacol Sci 108:135–139CrossRefPubMedGoogle Scholar
  66. 66.
    Sato T, Saito T, Saegusa N etal (2005) Mitochondrial Ca2+-activated K+ channels in cardiac myocytes. A mechanism of the cardioprotective effect and modulation by protein kinase A. Circulation 111:198–203CrossRefPubMedGoogle Scholar
  67. 67.
    Schubert R, Nelson MT (2001) Protein kinases: tuners of the BKCa channel in smooth muscle. Trends Pharmacol Sci 22:505–512CrossRefPubMedGoogle Scholar
  68. 68.
    Shi Y, Jiang MT, Su J etal (2007) Mitochondrial big conductance KCa channel and cardioprotection in infant rabbit heart. J Cardiovasc Pharmacol 50:497–502CrossRefPubMedGoogle Scholar
  69. 69.
    Siemen D, Loupatatzis C, Borecky J etal (1999) Ca2+-activated K channel of the BK-type in the inner mitochondrial membrane of a human glioma cell line. Biochem Biophys Res Commun 257:549–554CrossRefPubMedGoogle Scholar
  70. 70.
    Skalska J, Bednarczyk P, Piwonska M etal (2009) Calcium ions regulate K+ uptake into brain mitochondria: the evidence for a novel potassium channel. Int J Mol Sci 10:1104–1120CrossRefPubMedGoogle Scholar
  71. 71.
    Skalska J, Piwonska M, Wyroba E etal (2008) A novel potassium channel in skeletal muscle mitochondria. Biochim Biophys Acta 1777:651–659CrossRefPubMedGoogle Scholar
  72. 72.
    Soom M, Gessner G, Heuer H etal (2008) A mutually exclusive alternative exon of slo1 codes for a neuronal BK channel with altered function. Channels 2:278–282CrossRefPubMedGoogle Scholar
  73. 73.
    Stowe DF, Aldakkak M, Camara AKS etal (2006) Cardiac mitochondrial preconditioning by big Ca2+-sensitive K+ channel opening requires superoxide radical generation. Am J Physiol Heart Circ Physiol 290:H434–H440CrossRefPubMedGoogle Scholar
  74. 74.
    Szewczyk A, Kajma A, Malinska D etal (2010) Pharmacology of mitochondrial potassium channels: dark side of the field. FEBS Lett 584:2063–2069CrossRefPubMedGoogle Scholar
  75. 75.
    Valverde MA, Rojas P, Amigo J etal (1999) Acute activation of Maxi-K channels (hSlo) by estradiol binding to the β subunit. Science 285:1929–1931CrossRefPubMedGoogle Scholar
  76. 76.
    Wallner M, Meera P, Toro L (1996) Determinant for β-subunit regulation in high-conductance voltage-activated and Ca2+-sensitive K+ channels: an additional transmembrane region at the N terminus. Proc Natl Acad Sci USA 93:14922–14927CrossRefPubMedGoogle Scholar
  77. 77.
    Wang X, Fisher PW, Xi L etal (2008) Essential role of mitochondrial Ca2+-activated and ATP-­sensitive K+ channels in sildenafil-induced late cardioprotection. J Mol Cell Cardiol 44:105–113CrossRefPubMedGoogle Scholar
  78. 78.
    Wang X, Yin C, Xi L etal (2004) Opening of Ca2+-activated K+ channels triggers early and delayed preconditioning against I/R injury independent of NOS in mice. Am J Physiol Heart Circ Physiol 287:H2070–2077CrossRefPubMedGoogle Scholar
  79. 79.
    Wojtovich AP, Sherman TA, Nadtochiy SM (2011) SLO-2 is cytoprotective and contributes to mitochondrial potassium transport. PLoS One 6:e28287CrossRefPubMedGoogle Scholar
  80. 80.
    Wrzosek A (2009) Endothelium as target for large-conductance calcium-activated potassium channel openers. Acta Biochim Pol 56:393–404PubMedGoogle Scholar
  81. 81.
    Xu W, Liu Y, Wang S etal (2002) Cytoprotective role of Ca2+-activated K+ channels in the cardiac inner mitochondrial membrane. Science 298:1029–1033CrossRefPubMedGoogle Scholar
  82. 82.
    Yang Y, Jones AW, Thomas TR etal (2007) Influence of sex, high-fat diet, and exercise training on potassium currents of swine coronary smooth muscle. Am J Physiol Heart Circ Physiol 293:H1553–H1563CrossRefPubMedGoogle Scholar
  83. 83.
    Zhou XB, Wulfsen I, Utku E etal (2010) Dual role of protein kinase C on BK channel regulation. Proc Natl Acad Sci USA 107:8005–8010CrossRefPubMedGoogle Scholar
  84. 84.
    Zoratti M, De Marchi U, Gulbins E etal (2009) Novel channels in the inner mitochondrial membrane. Biochim Biophys Acta 1787:351–363CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of Developmental Cardiology, Institute of PhysiologyAcademy of Sciences of the Czech RepublicPragueCzech Republic

Personalised recommendations